Safety and Efficacy Study of GSK2838232 in Human Immunode... | NCT03045861

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cohort 1-GSK2838232 100 mg + Cobicistat 150 mg in Part A	Experimental	During Part A (Cohort 1), subjects will receive a single dose of GSK2838232 100 mg and Cobicistat 150 mg once daily each morning with a light breakfast meal and 240 mL of water from Day 1 to Day 10. Subjects will be followed up to Day 22.	Drug: GSK2838232 Drug: Cobicistat
Cohort 2-GSK2838232 200 mg + Cobicistat 150 mg in Part B	Experimental	During Part B (Cohort 2), subjects will receive a single dose of GSK2838232 200 mg and Cobicistat 150 mg once daily each morning with a light breakfast meal and 240 mL of water from Day 1 to Day 10. Subjects will be followed up to Day 22.	Drug: GSK2838232 Drug: Cobicistat
Cohort 3-GSK2838232 50 mg + Cobicistat 150 mg in Part B	Experimental	During Part B (Cohort 3), subjects will receive a single dose of GSK2838232 50 mg and Cobicistat 150 mg once daily each morning with a light breakfast meal and 240 mL of water from Day 1 to Day 10. Subjects will be followed up to Day 22.	Drug: GSK2838232 Drug: Cobicistat
Cohort 4-GSK2838232 20 mg + Cobicistat 150 mg in Part B	Experimental	During Part B (Cohort 4), subjects will receive a single dose of GSK2838232 20 mg and Cobicistat 150 mg once daily each morning with a light breakfast meal and 240 mL of water from Day 1 to Day 10. Subjects will be followed up to Day 22.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
GSK2838232	Drug	GSK2838232 capsules will be supplied as swedish orange, unmarked capsule (50 mg), and white, unmarked capsules (10 mg) in high-density polyethylene bottles.	Cohort 1-GSK2838232 100 mg + Cobicistat 150 mg in Part A

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Maximum Decline From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA)	Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. An HIV-1 RNA polymerase chain reaction (PCR) assay with a lower limit of detection (LLOD) of 50 copies/milliliter (ultrasensitive assay) was used for post-baseline assessments. Baseline value was the value at latest pre-dose assessment. The maximum decline was determined using change from Baseline in plasma HIV-RNA values at each time point. The analysis was performed on Intent To Treat (ITT) Population which comprised of all participants who met study criteria and were enrolled into the study with documented evidence of having received at least 1 dose of treatment and at least one post-Baseline HIV-1 RNA measurement.	Baseline (Day 1) to Day 21
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; other important medical events; is associated with liver injury and impaired liver function. Safety Population comprised of all participants who received at least one dose of study treatment.	Up to Day 22
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance	Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: carbon dioxide/bicarbonate (low: <18 millimoles per liter [mmol/L] and high: >32 mmol/L); urea (high: >9 mmol/L); creatinine (high: change from Baseline >44.2 micromoles per liter [µmol/L]), glucose (low: <3 and high: >9 mmol/L); potassium (low: <3 and high: >5.5 mmol/L); troponin I (high: >=0.01 micrograms per liter [µg/L]) and sodium (low: <130 mmol/L and high: >150 mmol/L). Data for any visit post-Baseline is reported.

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 AUC (0 to Tau)	Plasma samples were collected for quantitative analysis of HIV-1 RNA. Change from Baseline is the value at indicated time point minus Baseline value. Statistical analysis for relationship between pharmacokinetic parameters (AUC) and pharmacodynamic measures (Change from Baseline in plasma HIV-1 RNA) was explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: maximum response (Emax), pharmacokinetic parameter value that attains 50% of the maximal effect (ED50) and residual variability (s2e). Pharmacokinetic/Pharmacodynamic Population comprised of participants who met criteria for Per-Protocol (all participants who met study criteria and are enrolled into the study with documented evidence of having received all doses and all post-baseline HIV-1 RNA measurement, with exceptions of those who have at least one major protocol deviation) and Pharmacokinetic Population analysis sets and who underwent pharmacodynamic sampling during study.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Between 18 and 55 years of age inclusive, at the time of signing the informed consent.
Healthy (other than HIV infection) male or female as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring, defined as no other chronic medical conditions and taking no chronic medications.
A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator in consultation with the medical monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
A creatinine clearance >80 mL/minute as determined by Cockcroft-Gault equation creatinine clearance CLcr (mL/minute) = (140 - age) x weight (Wt) divided by (72 x serum creatinine [Scr]) (times 0.85 if female) where age is in years, Wt is in kilogram (kg), and Scr is in units of mg/decilitre (dL).
Confirmed HIV positive; CD4+ cell count >=350 cells/millimetre (mm)^3 and plasma HIV-1 RNA >=5000 copies/mL at screening.
No current and no prior ART.
Body weight >=50 kg (110 pound [lbs.]) for men and >=45 kg (99 lbs) for women and body mass index (BMI) within the range 18.5-31.0 kg/meter^2 (inclusive)
A female subject of reproductive or non-reproductive potential is eligible to participate if she is not pregnant (as confirmed by a negative serum or urine human chorionic gonadotrophin (hCG) test at screening and prior to first dose), not lactating, and at least one of the following conditions applies: females of reproductive potential may only be enrolled if they are using two forms of complementary contraception, which must include one barrier method. They will be counselled on safer sex practices; there is no definitive drug-drug interaction (DDI) information with GSK2838232 and an interaction with oral contraceptives is possible, so other (barrier, inter-uterine device etc.) methods of contraception will be required; fertile females, who have an established, long-term lifestyle of sexual abstinence, or only same sex partners, require no other means of birth control. Pre-menopausal females with one of the following: documented tubal ligation; documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; hysterectomy; documented bilateral oophorectomy; postmenopausal defined as 12 months of spontaneous amenorrhea in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT) must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until one week after the last dose of study medication; vasectomy with documentation of azoospermia; male condom plus partner use of one of the contraceptive options as: Contraceptive sub dermal implant including a <1 percent rate of failure per year; intrauterine device or intrauterine system including a <1 percent rate of failure per year; oral contraceptive, either combined or progestogen alone or injectable progestogen; contraceptive vaginal ring; percutaneous contraceptive patches. These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
Capable of giving signed informed consent.

Exclusion Criteria:

Alanine aminotransferase (ALT) and bilirubin (BIL) >1.5 x upper limit of normal (ULN), isolated BIL >1.5xULN is acceptable if BIL is fractionated and direct BIL <35 percent.
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones); hepatitis B virus (HBV) and/or hepatitis C virus (HCV) positive.
Subjects who have any other chronic medical condition, including cardiovascular (CV), respiratory, neurologic, psychiatric, renal, gastrointestinal (GI), oncologic, rheumatologic, or dermatologic.
Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK medical monitor the medication will not interfere with the study procedures or compromise subject safety.
History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 grams (g) of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
Smoking is an exclusion criteria for this study. Subject having urinary cotinine levels indicative of smoking at screening.
Chronic marijuana or use of other elicit medications (cocaine, heroin) is an exclusion criteria.
History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.
Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
Screening or Baseline cardiac troponin I greater than the 99 percent cutoff (>0.045 nanogram [ng]/mL by the Dimension Vista cardiac troponin [CTN] I assay).
A positive pre-study drug/alcohol screen.
Prior history of receiving an HIV maturation inhibitor
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days.
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 30 days of study drug administration or anticipated need for such treatment within the study.
Treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (such as hydroxyurea or foscarnet) within 30 days of study drug administration.
An active Center for Disease Control and Prevention (CDC) category C disease except cutaneous Kaposi's sarcoma not requiring systemic therapy during the trial.
Treatment with any vaccine within 30 days prior to receiving study medication.
Exclusion criteria for 24-hour screening holter: any symptomatic arrhythmia (except isolated extra systoles); sustained cardiac arrhythmias (such as atrial fibrillation, flutter or supraventricular tachycardia [>=10 seconds]); non-sustained or sustained ventricular tachycardia (defined as >=3 consecutive ventricular ectopic beats); any conduction abnormality including but not specific to left or complete bundle branch block, atrioventricular (AV) block, high grade or complete heart block Wolff-Parkinson-White (WPW) syndrome etc.; sinus pauses >3 seconds.
Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination): heart rate <45 and >100 beats per minute (bpm) for males, and <50 and >100 bpm for females; PR Interval <120 and >220 milliseconds (msec); QRS duration <70 and >120 msec; corrected QT (QTc) interval >450 msec; Evidence of previous myocardial infarction (Does not include ST segment changes associated with repolarization); any conduction abnormality (including but not specific to left or right complete bundle branch block, AV block [2nd degree or higher], WPW syndrome); sinus pauses >3 seconds; any significant arrhythmia which, in the opinion of the principal investigator or GSK medical monitor, will interfere with the safety for the individual subject; non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats).

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Birmingham	Alabama	35226	United States
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
31769793	Background	DeJesus E, Harward S, Jewell RC, Johnson M, Dumont E, Wilches V, Halliday F, Talarico CL, Jeffrey J, Gan J, Xu J, Felizarta F, Scribner A, Ramgopal M, Benson P, Johns BA. A Phase IIa Study Evaluating Safety, Pharmacokinetics, and Antiviral Activity of GSK2838232, a Novel, Second-generation Maturation Inhibitor, in Participants With Human Immunodeficiency Virus Type 1 Infection. Clin Infect Dis. 2020 Aug 22;71(5):1255-1262. doi: 10.1093/cid/ciz938.

ID	Title	Description
FG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
FG001	GSK2838232 50 mg

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 15, 2017	Apr 30, 2019

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Decline From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA)

Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. An HIV-1 RNA polymerase chain reaction (PCR) assay with a lower limit of detection (LLOD) of 50 copies/milliliter (ultrasensitive assay) was used for post-baseline assessments. Baseline value was the value at latest pre-dose assessment. The maximum decline was determined using change from Baseline in plasma HIV-RNA values at each time point. The analysis was performed on Intent To Treat (ITT) Population which comprised of all participants who met study criteria and were enrolled into the study with documented evidence of having received at least 1 dose of treatment and at least one post-Baseline HIV-1 RNA measurement.

ITT Population

Posted

Mean

Standard Deviation

Copies per milliliter

Baseline (Day 1) to Day 21

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG003	GSK2838232 200 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 200 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.

Units	Counts
Participants	OG0007 OG0018 OG00210 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-42095.14± 37575.520 OG001-49065.88± 71339.743 OG002-32947.50± 54291.492 OG003

Primary

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; other important medical events; is associated with liver injury and impaired liver function. Safety Population comprised of all participants who received at least one dose of study treatment.

Safety Population

Posted

Count of Participants

Participants

Up to Day 22

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002

Primary

Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance

Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: carbon dioxide/bicarbonate (low: <18 millimoles per liter [mmol/L] and high: >32 mmol/L); urea (high: >9 mmol/L); creatinine (high: change from Baseline >44.2 micromoles per liter [µmol/L]), glucose (low: <3 and high: >9 mmol/L); potassium (low: <3 and high: >5.5 mmol/L); troponin I (high: >=0.01 micrograms per liter [µg/L]) and sodium (low: <130 mmol/L and high: >150 mmol/L). Data for any visit post-Baseline is reported.

Safety Population

Posted

Count of Participants

Participants

Up to Day 22

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg

Primary

Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance

Blood samples were collected for the assessment of hematology parameters. The clinical concern range for the parameters were: hematocrit (high: >0.54 proportion of red blood cells in blood); hemoglobin (high: >180 grams per liter [g/L]), lymphocytes (low: <0.8x10^9 cells/L); neutrophil count (low: <1.5x10^9 cells/L); platelet count (low: <100x10^9 cells/L and high: >550x10^9 cells/L); white blood cells (low: <3x10^9 cells/L and high: >20x10^9cells/L). Data for any visit post-Baseline is reported.

Safety Population

Posted

Count of Participants

Participants

Up to Day 22

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg

Primary

Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance

Blood samples were collected for the assessment of liver function parameters. The clinical concern range for liver function parameters were: albumin (low: <30 g/L), total protein (low: <15 and high: >15 g/L), alanine aminotransferase (high: >=2 times upper limit of normal [ULN]); aspartate aminotransferase (high: >=2 times ULN); alkaline phosphatase (high: >=2 times ULN); total bilirubin (high: >=1.5 times ULN); direct bilirubin (high: >0.3 times ULN).

Safety Population

Posted

Count of Participants

Participants

Up to Day 22

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.

Primary

Number of Participants With Abnormal Urine Parameters

Urine samples were collected for the assessment of following urine parameters by dipstick method: pH, glucose, protein, blood and ketones. The number of participants with abnormal urine parameters is presented.

Safety Population

Posted

Count of Participants

Participants

Up to Day 22

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG003

Primary

Number of Participants With Abnormal Electrocardiogram (ECG) Findings

Triplicate 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT (QTc) intervals. Number of participants with abnormal ECG findings at worst-case post Baseline is presented.

Safety Population

Posted

Count of Participants

Participants

Up to Day 22

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.

Primary

Number of Participants With Vital Signs Data Outside Clinical Concern Range

Vital signs were measured in a semi-supine position after 5 minutes rest and included temperature, systolic and diastolic blood pressure and pulse rate. The clinical concern range for vital signs were: systolic blood pressure (SBP) (low: <85 and high: >160 millimeters of mercury [mmHg]) and diastolic blood pressure (DBP) (low: <45 and high: >100 mmHg). Number of participants with vital signs data outside clinical concern range is presented.

Safety Population

Posted

Count of Participants

Participants

Day 1 (pre-dose)

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.

Primary

Number of Participants Who Were Administered Concomitant Medications

Concomitant medications (prescription and non-prescription) were administered only as medically necessary during the study. Number of participants who received any concomitant medications is presented.

Safety Population

Posted

Count of Participants

Participants

Up to Day 22

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG003

Primary

Area Under the Plasma Concentration Time Curve From Zero (Pre-dose) to 24 Hours (AUC[0 to 24]) for GSK2838232 on Day 1

Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232. The analysis was performed on Pharmacokinetic Population which comprised of participants who received GSK2838232 and underwent plasma pharmacokinetic sampling during the study.

Pharmacokinetic Population. One participant from GSK2838232 100 mg arm was dosed with GSK2838232 50 mg on Days 1 and 2; hence, pharmacokinetic parameters for that participant were summarized with GSK2838232 50 mg for Day 1

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours*nanograms per milliliter

Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 1

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg

Primary

Maximum Observed Concentration (Cmax) for GSK2838232 on Day 1

Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanograms per milliliter

Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 1

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.

Primary

Time to Maximum Observed Concentration (Tmax) for GSK2838232 on Day 1

Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.

Posted

Median

Full Range

Hours

Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 1

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.

Primary

Absorption Lag Time (Tlag) for GSK2838232 on Day 1

Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.

Posted

Median

Full Range

Hours

Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 1

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.

Primary

Concentration of GSK2838232 at 24 Hours Post-dose on Day 1

Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanograms per milliliter

24 hours post-dose on Day 1

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.

Primary

Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0 to Tau]) for GSK2838232 on Day 10

Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.

Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours*nanograms per milliliter

Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 10

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.

Primary

Pre-dose Concentration (C0) of GSK2838232 on Day 10

Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.

Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanograms per milliliter

Pre dose on Day 10

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG003

Primary

Concentration at End of Dosing Interval (Ctau) for GSK2838232 on Day 10

Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.

Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanograms per milliliter

24 hours post-dose on Day 10

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.

Primary

Cmax for GSK2838232 on Day 10

Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.

Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanograms per milliliter

Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 10

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.

Primary

Apparent Oral Clearance of GSK2838232 Following Administration on Day 10

Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.

Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Liters per hour

Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 10

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.

Primary

Terminal Elimination Half-life (T1/2) of GSK2838232 Following Administration on Day 10

Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.

Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours

Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 10

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.

Primary

Tmax for GSK2838232 Following Administration on Day 10

Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.

Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.

Posted

Median

Full Range

Hours

Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 10

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.

Secondary

Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 AUC (0 to Tau)

Plasma samples were collected for quantitative analysis of HIV-1 RNA. Change from Baseline is the value at indicated time point minus Baseline value. Statistical analysis for relationship between pharmacokinetic parameters (AUC) and pharmacodynamic measures (Change from Baseline in plasma HIV-1 RNA) was explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: maximum response (Emax), pharmacokinetic parameter value that attains 50% of the maximal effect (ED50) and residual variability (s2e). Pharmacokinetic/Pharmacodynamic Population comprised of participants who met criteria for Per-Protocol (all participants who met study criteria and are enrolled into the study with documented evidence of having received all doses and all post-baseline HIV-1 RNA measurement, with exceptions of those who have at least one major protocol deviation) and Pharmacokinetic Population analysis sets and who underwent pharmacodynamic sampling during study.

Pharmacokinetic/Pharmacodynamic Population

Posted

Mean

Standard Deviation

log10 copies per milliliter

Baseline (Day 1), Days 10 and 11

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg

Secondary

Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 Cmax

Plasma samples were collected for quantitative analysis of HIV-1 RNA. Change from Baseline is the value at indicated time point minus Baseline value. Statistical analysis for the relationship between pharmacokinetic parameters (Cmax) and pharmacodynamic measures (change from Baseline in log10 plasma HIV-1 RNA) was explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: maximum response (Emax), pharmacokinetic parameter value that attains the 50% of the maximal effect (ED50) and s2e.

Pharmacokinetic/Pharmacodynamic Population.

Posted

Mean

Standard Deviation

log10 copies per milliliter

Baseline (Day 1), Days 10 and 11

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg

Secondary

Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 Ctau

Plasma samples were collected for quantitative analysis of HIV-1 RNA. Change from Baseline is the value at indicated time point minus Baseline value. Statistical analysis for the relationship between pharmacokinetic parameters (Ctau) and pharmacodynamic measures (change from Baseline in log10 plasma HIV-1 RNA) was explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: maximum response (Emax), pharmacokinetic parameter value that attains the 50% of the maximal effect (ED50) and s2e.

Pharmacokinetic/Pharmacodynamic Population.

Posted

Mean

Standard Deviation

log10 copies per milliliter

Baseline (Day 1), Days 10 and 11

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg

Secondary

Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Count to Day 11

CD4+ cell counts were assessed by flow cytometry. Baseline value is the latest pre-dose assessment value. Change from Baseline is calculated as the post-dose visit value minus Baseline value.

ITT Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Cells per microliter

Baseline (Day 1) and Day 11

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.

Secondary

Change From Baseline to Day 11 in CD4+ Count Relative to Day 10 AUC (0 to Tau)

The relationship between pharmacokinetic parameters (AUC) and pharmacodynamic measures (change from Baseline CD4+ cell count) was explored using a frequentist linear model. The model parameters estimated included slope and intercept. The estimate (slope) along with 95% confidence interval is presented.

Pharmacokinetic/Pharmacodynamic Population

Posted

Number

95% Confidence Interval

cells/microliter/ng*h/mL

Baseline (Day 1), Days 10 and 11

ID	Title	Description
OG000	Participants Receiving GSK2838232	Participants who received GSK2838232 at doses of 20 mg, 50 mg, 100 mg and 200 mg were included.

Units	Counts
Participants	OG000

Secondary

Change From Baseline to Day 11 in CD4+ Count Relative to Day 10 Cmax

The relationship between pharmacokinetic parameters (Cmax) and pharmacodynamic measures (change from Baseline CD4+ cell count) was explored using a frequentist linear model. The model parameters estimated included slope and intercept. The estimate (slope) along with 95% confidence interval is presented

Pharmacokinetic/Pharmacodynamic Population

Posted

Number

95% Confidence Interval

cells/microliter/nanograms/milliliter

Baseline (Day 1), Days 10 and 11

ID	Title	Description
OG000	Participants Receiving GSK2838232	Participants who received GSK2838232 at doses of 20 mg, 50 mg, 100 mg and 200 mg were included.

Units	Counts
Participants	OG000

Secondary

Change From Baseline to Day 11 in CD4+ Count Relative to Day 10 Ctau

The relationship between pharmacokinetic parameters (Ctau) and pharmacodynamic measures (change from Baseline CD4+ cell count) was explored using a frequentist linear model. The model parameters estimated included slope and intercept. The estimate (slope) along with 95% confidence interval is presented.

Pharmacokinetic/Pharmacodynamic Population

Posted

Number

95% Confidence Interval

cells/microliter/nanograms/milliliter

Baseline (Day 1), Days 10 and 11

ID	Title	Description
OG000	Participants Receiving GSK2838232	Participants who received GSK2838232 at doses of 20 mg, 50 mg, 100 mg and 200 mg were included.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Emergent Drug Resistance Mutations

Plasma samples were collected to evaluate treatment-emergent genotypic mutations in Gag, reverse transcriptase (RT) and protease (PR) and to assess phenotypic resistance to GSK2838232 and RT and PR drugs. Number of participants with treatment emergent RT/PR mutations, reduced susceptibility to nucleoside/nucleotide reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or protease inhibitor (PI), treatment emergent maturation inhibitor A364A/V and GSK2838232 phenotypic resistance is presented.

ITT Population

Posted

Count of Participants

Participants

Up to Day 11

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg

Secondary

Accumulation Ratio for GSK2838232

Serial blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232. The accumulation ratios were calculated as R_AUC=AUC(0-tau) Day 10/AUC(0-24) Day 1; R_Cmax=Cmax Day 10/Cmax Day 1 and R_Ctau=Ctau Day 10/C24 Day 1.

Pharmacokinetic Population. Only participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Ratio

pre dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Days 1 and 10; pre-dose on Days 3, 4, 5, 8 and 9; Days 12 and 14

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.

Secondary

Dose Proportionality of GSK2838232

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232. Dose proportionality was assessed using a fixed effects power model. Estimated slope and 90% confidence interval is presented.

Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category )

Posted

Number

90% Confidence Interval

slope of log dose

pre dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Days 1 and 10

ID	Title	Description
OG000	Participants Receiving GSK2838232	Participants who received GSK2838232 at doses of 20 mg, 50 mg, 100 mg and 200 mg were included.

Units	Counts
Participants	OG000

Secondary

Pre-morning Dose Concentrations (C0) on Day 2 Through 11

Blood samples were collected for pharmacokinetic analysis of GSK2838232. The pre-morning dose concentrations for Days 2 to 11 is presented. One participant from GSK2838232 100 mg arm was dosed with GSK2838232 50 mg on Days 1 and 2; hence, pharmacokinetic parameters for that participant were summarized with GSK2838232 50 mg for Days 1 and 2 and with GSK2838232 100 mg for Days 3 to 10.

Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles)

Posted

Mean

Standard Deviation

Nanograms per milliliter

Pre-dose on Days 2, 3, 4, 5, 8, 9, 10 and 11

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg

Secondary

Steady State Assessment of Plasma Pre-dose Concentrations by Treatment

A linear mixed model using Day, treatment and Day by treatment as fixed effects and participant as a random effect on the log-transformed pre-dose values was performed to evaluate if steady state was achieved using the Helmert transformation approach. The comparison was done as Day 8 versus the average of Days 9 and 10 values. The ratio of geometric least square mean for Day 8 versus average of Days 9 and 10 values is presented along with 95% confidence interval.

Pharmacokinetic Population

Posted

Number

95% Confidence Interval

Ratio

Pre-dose on Days 8, 9 and 10

ID	Title	Description
OG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
OG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
OG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected8 at risk EG0022 events2 affected10 at risk EG0030 events0 affected8 at risk
Dizziness	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected8 at risk EG0020 events0 affected10 at risk EG003
Head discomfort	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected8 at risk EG0020 events0 affected10 at risk EG003
Presyncope	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected8 at risk EG0020 events0 affected10 at risk EG003
Somnolence	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected8 at risk EG0021 events1 affected10 at risk EG003
Acne	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected8 at risk EG0020 events0 affected10 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected8 at risk EG0020 events0 affected10 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected8 at risk EG0020 events0 affected10 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected8 at risk EG0021 events1 affected10 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected8 at risk EG0020 events0 affected10 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected8 at risk EG0020 events0 affected10 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected8 at risk EG0020 events0 affected10 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected8 at risk EG0020 events0 affected10 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected8 at risk EG0021 events1 affected10 at risk EG003
Fatigue	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected8 at risk EG0020 events0 affected10 at risk EG003
Medical device site dermatitis	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected8 at risk EG0020 events0 affected10 at risk EG003
Medical device site reaction	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected8 at risk EG0020 events0 affected10 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected8 at risk EG0020 events0 affected10 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected8 at risk EG0020 events0 affected10 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected8 at risk EG0020 events0 affected10 at risk EG003
Abnormal dreams	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected8 at risk EG0020 events0 affected10 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected8 at risk EG0020 events0 affected10 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected8 at risk EG0021 events1 affected10 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected8 at risk EG0020 events0 affected10 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected8 at risk EG0021 events1 affected10 at risk EG003

ID	Term
D007239	Infections
D000163	Acquired Immunodeficiency Syndrome
D015658	HIV Infections

ID	Term
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D015229	Sexually Transmitted Diseases, Viral
D012749	Sexually Transmitted Diseases
D016180	Lentivirus Infections
D012192	Retroviridae Infections
D012327	RNA Virus Infections
D014777	Virus Diseases
D012897	Slow Virus Diseases
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D007153	Immunologic Deficiency Syndromes
D007154	Immune System Diseases

ID	Term
D002219	Carbamates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D013844	Thiazoles
D013457	Sulfur Compounds
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds

ID	Title	Description
BG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.
BG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
BG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
BG003	GSK2838232 200 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 200 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.
BG004	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	GSK2838232 20 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10.	7	7	3	7
EG001	GSK2838232 50 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.	8	8	3	8
EG002	GSK2838232 100 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.	10	10	5	10
EG003	GSK2838232 200 mg	Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 200 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10.	8	8	5	8